The Organic Chemistry of Drug Synthesis

THE ORGANIC CHEMISTRY OF DRUG SYNTHESIS Volume DANIEL LEDNICER North Bethesda, MD THE ORGANIC CHEMISTRY OF DRUG SYNTHESIS THE ORGANIC CHEMISTRY OF DRUG SYNTHESIS Volume DANIEL LEDNICER North Bethesda, MD Copyright # 2008 by John Wiley & Sons, Inc All rights reserved Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate percopy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the Web at www.copyright.com Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008, or online at http://www wiley.com/go/permission Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose No warranty may be created or extended by sales representatives or written sales materials The advice and strategies contained herein may not be suitable for your situation You should consult with a professional where appropriate Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002 Wiley also publishes it books in variety of electronic formats Some content that appears in print may not be available in electronic formats For more information about Wiley products, visit our web site at www.wiley.com Wiley Bicentennial Logo: Richard J Pacifico Library of Congress Cataloging-in-publication Data is available ISBN 978-0-470-10750-8 Printed in the United States of America 10 To the memory of I Moyer Hunsberger and Melvin S Newman who set me on course CONTENTS Preface xi OPEN-CHAIN COMPOUNDS Peptidomimetic Compounds / A Antiviral Protease Inhibitors / Human Immunodeficiency Virus / 2 Human Rhinovirus / Miscellaneous Peptidomimetic Compounds / 11 References / 19 ALICYCLIC COMPOUNDS 21 Monocyclic Compounds / 21 A Prostaglandins / 21 B Antiviral Agents / 25 C Miscellaneous Monocyclic Compounds / 29 Polycyclic Compounds: Steroids / 31 A 19-Nor Steroids / 31 B Corticosteroid Related Compounds / 34 vii 258 CUMULATIVE INDEX Hydrocodone, 1, 288 Hydrocortisone, 1, 190 Hydrocortisone acetate, 1, 190 Hydroflumethiazide, 1, 358 Hydromorphone, 1, 288 Hydroxyamphetamine, 1, 71 Hydroxychloroquine, 1, 342 Hydroxyphenamate, 1, 220 Hydroxyprocaine, 1, 11 Hydroxyprogesterone, 1, 176 Hydroxyzine, 1, 59 Ibafloxacin, 5, 127 Ibrolipim, 7, 44 Ibufenac, 1, 86 Ibuprofen, 1, 86 Ibutamoren, 7, 153 Ibutilide, 5, 23 Iclaprim, 7, 125 Icopezil, 6, 137 Icotidine, 4, 113 Idarubicin, 5, 47 Idoxifene, 6, 44 Ifenprodil, 2, 39 Ifetroban, 6, 93 Ifosfamide, 3, 151 Igmesine, 7, 64 Ilepcimide, 6, 42 Ilmofosine, 6, 26 Ilonidap, 6, 133 Iloperidone, 6, 103 Imafen, 3, 226 Imazodan, 4, 90 Imidoline, 2, 259 Imiloxan, 4, 88 Imipenem, 4, 181 Imipramine, 1, 401 Imiquimod, 5, 173 Imolamine, 1, 249 Indacrinone, 3, 67 Indapamide, 2, 349 Indecainide, 4, 62 Indeloxazine, 4, 59 Indinavir, 6, 12 Indiplon, 7, 192 Indolapril, 4, 128 Indolidan, 5, 117 Indomethacin, 1, 318 Indoprofen, 3, 171 Indoramine, 2, 344 Indorenate, 3, 167 Indoxole, 2, 254 Inocoterone, 5, 49 Intrazole, 2, 354 Intriptyline, 2, 223 Iodothiouracil, 1, 265 Ipazilide, 5, 70 Ipexidine, 3, 157 Ipratropium bromide, 3, 160 Iprindol, 1, 318 Iproniazide, 1, 254 Ipronidazole, 2, 244 Iproplatin, 4, 17 Ipsapirone, 5, 91 Irbesartan, 6, 23 Irinotecan, 6, 206 Irofulven, 7, 38 Irtemazole, 5, 117 Isamoxole, 3, 138 Isatoribine, 7, 207 Isbogrel, 6, 42 Isoaminile, 1, 82 Isobucaine, 1, 12 Isobuzole, 2, 272 Isocarboxazide, 1, 233 Isoetharine, 2, Isomazole, 4, 163 Isomethadone, 1, 79 Isomylamine, 2, 11 Isoniazide, 1, 254 Isopentaquine, 1, 346 Isoproteronol, 1, 63 Isoproteronol, 5, 15 Isopyrine, 1, 234 Isothipendyl, 1, 430 Isotiquamide, 4, 139 Isotretinoin, 3, 12 Isoxepac, 3, 328 Isoxicam, 2, 394 Isoxsuprine, 1, 69 Isradipine, 4, 107 Istradefylline, 7, 202 Itasetron, 6, 141 Itazigrel, 4, 96 Izonsteride, 7, 223 CUMULATIVE INDEX Ketamine, 1, 57 Ketanserin, 3, 193 Ketasone, 1, 237 Ketazocine, 2, 238 Ketazolam, 1, 369 Ketobemidone, 1, 303 Ketoconazole, 3, 132 Ketoprofen, 2, 64 Ketorfanol, 4, 60 Ketorolac, 4, 81 Ketotifen, 3, 239 Khellin, 1, 313 Labetolol, 3, 24 Lacidipine, 5, 82 Lacosamide, 7, 14 Ladostigil, 7, 71 Lamifiban, 6, 19 Lamivudine, 5, 99 Lamotrigine, 4, 120 Lanoconazole, 6, 75 Lansoprazole, 5, 115 Lapatinib, 7, 182 Lasofoxifene, 7, 77 Latanoprost, 6, 52 Latanoprost, 7, 23 Lavoltidine, 5, 77 Lazabemide, 6, 95 Lecimibide, 6, 78 Leflunomide, 7, 93 Lenalidomide, 7, 153 Leniquinsin, 2, 363 Lenperone, 2, 286 Lergotrile, 2, 480 Leteprinim, 7, 202 Letimide, 2, 393 Letrozole, 6, 86 Levalorphanol, 1, 293 Levamisole, 4, 217 Levarterenol, 1, 63 Levcromakalim, 6, 147 Levocabastine, 4, 110 Levonantrodol, 3, 188 Levonordefrine, 1, 68 Levophenacylmorphan, 1, 294 Levopropoxyphene, 1, 50 Levothyroxine, 1, 97 Lexipafant, 6, 177 Liarozole, 6, 76 Lidamidine, 3, 56 Lidocaine, 1, 16 Lidoflazine, 1, 279 Lidorestat, 7, 145 Lifarizine, 5, 92 Lifibrate, 1, 103 Lilopristone, 6, 65 Linarotene, 5, 37 Linezolid, 6, 74 Linogrilide, 4, 80 Linopirdine, 6, 134 Liothyronine, 1, 97 Lisinopril, 4, 83 Lisofylline, 6, 177 Lixazinone, 5, 166 Lixivaptan, 7, 222 Lobendazole, 2, 353 Lobenzarit, 4, 43 Lobucavir, 6, 186 Lodelaben, 5, 22 Lodoxamide, 3, 57 Lofemizole, 4, 90 Lofentanyl, 3, 117 Lofepramine, 4, 201 Lofexidine, 4, 88 Lomefloxacin, 5, 125 Lometraline, 2, 214 Lometrexol, 5, 151 Lomustine, 2, 12 Lonapalene, 4, 57 Loperamide, 2, 334 Lopinavir, 7, Loracarbef, 5, 162 Loratidine, 4, 200 Lorazepam, 1, 368 Lorbamate, 2, 21 Lorcainide, 3, 40 Lorcinadol, 5, 94 Loreclezole, 5, 78 Lorglumide, 5, 20 Lormetazepam, 3, 196 Lornoxicam, 6, 188 Lortalamine, 4, 404 Lorzafone, 4, 48 Losartan, 5, 73 Losoxantrone, 5, 43 Losulazine, 4, 139 259 260 CUMULATIVE INDEX Loteprednol, 5, 56 Lovastatin, 5, 88 Loviride, 6, 48 Loxapine, 2, 427 Loxoribine, 5, 145 Lubazodone, 7, 70 Lubeluzole, 7, 160 Lubiprostone, 7, 23 Lucanthone, 1, 397 Lufironil, 6, 95 Lupitidine, 4, 115 Lurosetron, 6, 194 Lurtotecan, 6, 208 Lynestrol, 1, 166 Mafenide, 2, 114 Mafosfamide, 5, 102 Malotilate, 5, 75 Maprotiline, 2, 220 Maraviroc, 7, 107 Maribavir, 7, 158 Marimastat, 6, 15 Maropitant, 7, 62 Masoprocol, 5, 31 Mazapertine, 6, 114 Mazindol, 2, 462 Mebendazole, 2, 353 Mebeverine, 2, 54 Mebhydroline, 1, 319 Mebromphenhydramine, 1, 44 Mebutamate, 1, 218 MeCCNU, 2, 12 Mecillinam, 3, 208 Meclastine, 1, 44 Meclizine, 1, 59 Meclofenamic acid, 1, 110 Meclorisone butyrate, 3, 95 Medazepam, 1, 368 Medetomidine, 5, 71 Medibazine, 2, 30 Mediquox, 2, 390 Medorinone, 5, 149 Medrogestone, 1, 182 Medroxalol, 3, 25 Medroxyprogesterone, 1, 180 Medrylamine, 1, 41 Medrysone, 2, 200 Mefenamic acid, 1, 110 Mefenidil, 4, 89 Mefenorex, 2, 47 Mefexamide, 2, 103 Mefruside, 1, 134 Megesterol acetate, 1, 180 Melagartan, 7, 16 Melengesterol acetate, 1, 182 Melitracen, 2, 220 Melphalan, 2, 120 Memotine, 2, 378 Menabitan, 4, 210 Menoctone, 2, 217 Meobentine, 3, 45 Meparfynol, 1, 38 Meperidine, 1, 300 Mephenhydramine, 1, 44 Mephenoxalone, 1, 119 Mephensin, 1, 118 Mephensin carbamate, 1, 118 Mephentermine, 1, 72 Mephenytoin, 1, 246 Mephobarbital, 1, 273 Mepivacaine, 1, 17 Meprobamate, 1, 218 Mequoqualone, 1, 354 Meralluride, 1, 224 Mercaptomerine, 1, 224 Meropenem, 6, 164 Meseclazone, 1, 254 Mesoridazine, 1, 389 Mesterolone, 1, 174 Mestranol, 1, 162 Mesuprine, 2, 41 Metabutoxycaine, 1, 11 Metalol, 2, 41 Metampicillin, 1, 41 Metaproterenol, 1, 64 Metaxalone, 1, 119 Meteneprost, 3, Metesind, 6, 200 Methacycline, 2, 227 Methadone, 1, 79 Methallenestril, 1, 187 Methamphetamine, 1, 37 Methandrostenolone, 1, 173 Methantheline bromide, 1, 393 Methaphencycline, 1, 53 Methaphenyline, 1, 52 CUMULATIVE INDEX Methaprylon, 1, 259 Methapyriline, 1, 54 Methaqualone, 1, 353 Metharbital, 1, 273 Methazolamide, 1, 250 Methdilazine, 1, 387 Methenolone acetate, 1, 175 Methicillin, 1, 412 Methimazole, 1, 240 Methisazone, 2, 350 Methitural, 1, 275 Methixine, 1, 400 Methocarbamol, 1, 118 Methohexital, 1, 269 Methopholine, 1, 349 Methopromazine, 1, 374 Methoxsalen, 1, 333 Methoxypromazine, 1, 387 Methsuximide, 1, 228 Methyclothiazide, 1, 360 Methylchromone, 1, 335 Methyldihydromorphinone, 1, 292 Methyldopa, 1, 95 Methylphenidate, 1, 88 Methylprednisolone, 1, 193 Methyltestosterone, 1, 172 Methylthiouracil, 1, 264 Methynodiol diacetate, 2, 149 Methyridine, 1, 256 Methysergide, 2, 477 Metiamide, 2, 252 Metiapine, 2, 429 Metioprim, 3, 155 Metipronalol, 5, 17 Metizoline, 2, 256 Metoclopramide, 5, 20 Metolazone, 2, 384 Metopimazine, 1, 153 Metoprolol, 2, 109 Metrenperone, 5, 150 Metronidazole, 1, 240 Mexrenoate, 2, 175 Mexrenone, 2, 175 Mezlocillin, 3, 206 Mianserin, 2, 451 Mibefradil, 6, 61 Mibolerone, 2, 144 Miconazole, 2, 249 Midaflur, 2, 259 Midazolam, 3, 197 Midodrine, 4, 23 Mifepristone, 5, 53 Miglitol, 6, 100 Milameline, 6, 98 Milenperone, 3, 172 Milipertine, 2, 341 Mimbane, 2, 347 Minalrestat, 6, 157 Minaprine, 4, 120 Minaprine, 5, 96 Minaxolone, 3, 90 Minocycline, 1, 214 Minoxidil, 1, 262 Mioflazine, 4, 119 Mirfentanil, 6, 101 Mirisetron, 6, 155 Mirtazapine, 5, 177 Misonidazole, 3, 132 Mitindomine, 4, 218 Mitoxantrone, 3, 75 Mivobulin, 6, 188 Mixidine, 2, 54 Moclobemide, 4, 39 Modafinil, 6, 38 Modaline, 2, 299 Modecainide, 5, 86 Moexipril, 6, 156 Mofebutazone, 1, 234 Mofegiline, 6, 35 Molinazone, 2, 395 Molindone, 2, 455 Molsidomine, 3, 140 Mometasone, 4, 73 Monasterol, 7, 128 Monatepil, 6, 198 Montelukast, 6, 150 Moprolol, 2, 109 Morantel, 1, 266 Morazone, 2, 261 Moricizine, 4, 200 Morniflumate, 3, 146 Morphazineamide, 1, 277 Morphedrine, 1, 300 Morphine, 1, 286 Motretinide, 3, 12 Moxalactam, 3, 218 261 262 CUMULATIVE INDEX Moxazocine, 3, 114 Moxisylyte, 1, 116 Moxnidazole, 2, 246 Mubritinib, 7, 108 Muraglitazar, 7, 47 Muzolimine, 3, 137 Nabazenil, 4, 209 Nabilone, 3, 189 Nabitan, 3, 190 Naboctate, 4, 209 Nadolol, 2, 110 Nafamostat, 6, 59 Nafcillin, 1, 412 Nafenopin, 2, 214 Nafimidone, 4, 90 Naflocort, 4, 75 Nafomine, 2, 212 Nafoxidine, 1, 147 Nafronyl, 2, 213 Naftidine, 3, 372 Naftifine, 4, 55 Nalbufine, 2, 319 Nalidixic acid, 1, 429 Nalmefene, 4, 62 Nalmexone, 2, 319 Nalorphine, 1, 288 Naloxone, 1, 289 Naltrexone, 2, 319 Namindinil, 7, 51 Namoxyrate, 1, 86 Nandrolone, 1, 164 Nandrolone decanoate, 1, 171 Nandrolone phenpropionate, 1, 171 Nantradol, 3, 186 Napactidine, 3, 71 Napamazole, 4, 87 Naphazoline, 1, 241 Napitane, 6, 60 Naproxen, 1, 86 Napsagatran, 6, 17 Naranol, 2, 454 Naratriptan, 6, 128 Nateglinide, 7, 15 Naxifylline, 7, 203 Naxogilide, 5, 175 Nebivolol, 5, 128 Nedocromil, 4, 209 Nefazodone, 4, 98 Neflumozide, 4, 133 Nefopam, 2, 447 Nelarabine, 7, 200 Nelezaprine, 5, 168 Nelfinavir, 6, Nemazoline, 6, 79 Neostigmine, 1, 114 Nepicastat, 7, 97 Nequinate, 2, 369 Netobimin, 4, 36 Netoglitazone, 7, 103 Nevirapine, 6, 199 Nexeridine, 2, 17 Nialamide, 1, 254 Nicardipine, 3, 150 Nicergoline, 2, 478 Niclosamide, 2, 94 Nicordanil, 3, 148 Nicotinic acid, 1, 253 Nictotinyl alcohol, 1, 253 Nidroxyzone, 1, 228 Nifedipine, 2, 283 Nifenazone, 1, 234 Nifluminic acid, 1, 256 Nifuratrone, 2, 238 Nifurdazil, 2, 239 Nifurimide, 2, 239 Nifuroxime, 2, 238 Nifurpirinol, 2, 240 Nifurprazine, 1, 231 Nifurquinazol, 2, 383 Nifursemizone, 2, 238 Nifurthiazole, 2, 241 Nikethamide, 1, 253 Nilutamide, 6, 46 Nilvadipine, 4, 107 Nimazone, 2, 260 Nimodipine, 3, 149 Nimorazole, 2, 244 Niridazole, 2, 269 Nisbuterol, 3, 23 Nisobamate, 2, 22 Nisoxetine, 3, 32 Nistremine acetate, 3, 88 Nitazoxinide, 7, 101 Nithiazole, 2, 268 Nitisinone, 7, 47 CUMULATIVE INDEX Nitrafudam, 3, 130 Nitrazepam, 1, 366 Nitrimidazine, 1, 240 Nitrofurantel, 1, 229 Nitrofurantoin, 1, 230 Nitrofurazone, 1, 229 Nitrofuroxime, 1, 228 Nitromifene, 3, 51 Nivazol, 2, 159 Nivimedone, 3, 67 Nizatidine, 4, 95 Noberastine, 5, 144 Noberastine, 6, 139 Nocodazole, 3, 176 Nomifensine, 4, 146 Noracylmethadol, 2, 58 Norbolethone, 2, 151 Norelgestimate, 7, 34 Norephedrine, 1, 260 Norethandrolone, 1, 170 Norethindrone, 1, 164 Norethindrone acetate, 1, 165 Norethynodrel, 1, 168 Norfloxacin, 4, 141 Norgestatriene, 1, 168 Norgestatrienone, 1, 186 Norgestrel, 1, 167 Normeperidine, 1, 300 Normethadone, 1, 81 Normethandrolone, 1, 170 Norpipanone, 1, 81 Nortriptyline, 1, 151 Nufenoxole, 3, 42 Nylidrin, 1, 69 Ocaperidone, 6, 103 Ocfentanil, 5, 83 Ocinaplon, 6, 173 Octazamide, 2, 448 Octopamine, 5, 23 Octriptyline, 2, 223 Ofloxacin, 4, 141 Ofornine, 4, 102 Oglufanide, 7, 142 Olanzapine, 5, 169 Olmesartan, 7, 111 Olopatadine, 6, 97 Olsalazine, 4, 42 Olvanil, 4, 35 Omaciclovir, 7, 199 Omapatrilat, 7, 191 Omeprazole, 4, 133 Omoconazole, 7, 94 Onapristone, 5, 53 Ondansetron, 5, 164 Ontazolast, 6, 137 Orbofiban, 6, 21 Orconazole, 3, 133 Orfadin, 7, 47 Orlistat, 6, 28 Ormaplatin, 5, 11 Ormetoprim, 2, 302 Ornidazole, 3, 131 Orpanoxin, 3, 130 Orphenadrine, 1, 42 Oseltamivir, 7, 25 Ospemifene, 7, 65 Oxacephalothin, 1, 420 Oxacillin, 1, 413 Oxagrelate, 4, 151 Oxamisole, 5, 14 Oxamniquine, 2, 372 Oxanamide, 1, 220 Oxandrolone, 1, 174 Oxantel, 2, 303 Oxaprotiline, 4, 63 Oxaprozin, 2, 263 Oxarbazole, 3, 169 Oxatomide, 3, 173 Oxazepam, 1, 366 Oxazolapam, 1, 370 Oxeladin, 1, 90 Oxendolone, 4, 66 Oxethazine, 1, 72 Oxetorene, 3, 247 Oxfendazole, 2, 353 Oxibendazole, 2, 352 Oxiconazole, 5, 72 Oxifungin, 3, 233 Oxilorphan, 2, 325 Oximonam, 4, 195 Oxiperomide, 2, 290 Oxiramide, 3, 40 Oxisuran, 2, 280 Oxmetidine, 3, 134 Oxolamine, 1, 248 263 264 CUMULATIVE INDEX Oxolinic acid, 2, 370 Oxprenolol, 1, 117 Oxybutynin, 1, 93 Oxycodone, 1, 290 Oxyfedrine, 2, 40 Oxymestrone, 1, 173 Oxymetazoline, 1, 242 Oxymetholone, 1, 173 Oxymorphone, 1, 290 Oxypendyl, 1, 430 Oxypertine, 2, 343 Oxyphenbutazone, 1, 236 Oxyphencyclimine, 2, 75 Oxyphenisatin, 2, 350 Oxypurinol, 1, 426 Oxytetracycline, 1, 212 Ozolinone, 3, 140 Pagoclone, 6, 136 Palinavir, 6, 10 Paliperidone, 7, 209 Palmoxiric acid, 4, Palonosetron, 6, 201 Paludrine, 1, 115 Pamaquine, 1, 345 Pamatolol, 3, 28 Panadiplon, 5, 173 Pancopride, 5, 21 Pancuronium chloride, 2, 163 Pantoprazole, 5, 115 Papaverine, 1, 347 Para aminosalicylic acid, 1, 109 Paraethoxycaine, 1, 10 Paramethadione, 1, 232 Paramethasone, 1, 200 Paranyline, 2, 218 Parapenzolate bromide, 2, 75 Parconazole, 3, 133 Parecoxib, 7, 92 Pargyline, 1, 54 Paroxetine, 5, 87 Pazinaclone, 6, 135 Pazoxide, 2, 395 Pecazine, 1, 387 Pefloxacin, 4, 141 Pelanserin, 5, 94 Peldesine, 6, 173 Pelitinib, 7, 167 Pelitrexol, 7, 212 Pelretin, 5, Pelrinone, 4, 116 Pemedolac, 5, 165 Pemerid, 2, 288 Pemetrexed, 7, 193 Pemirolast, 5, 150 Penciclovir, 6, 183 Penfluridol, 2, 334 Pentamorphone, 5, 42 Pentapiperium, 2, 76 Pentaquine, 1, 346 Pentazocine, 1, 297 Pentethylcyclanone, 1, 38 Pentiapine, 4, 220 Pentizidone, 4, 86 Pentobarbital, 1, 268 Pentomone, 3, 248 Pentopril, 4, 128 Pentoxiphyline, 2, 466 Pentylenetetrazole, 1, 281 Peramavir, 7, 53 Perazine, 1, 381 Perfosfamide, 5, 102 Pergolide, 3, 249 Perindopril, 5, 111 Perlapine, 2, 425 Perphenazine, 1, 383 Perzinfotel, 7, 39 Pethidine, 1, 300 Phenacaine, 1, 19 Phenacemide, 1, 95 Phenacetin, 1, 111 Phenadoxone, 1, 80 Phenaglycodol, 1, 219 Phenazocine, 1, 298 Phenazopyridine, 1, 255 Phenbencillin, 1, 410 Phenbenzamine, 2, 50 Phenbutalol, 2, 110 Phencarbamide, 2, 97 Phencyclidine, 1, 56 Phendimetrazine, 1, 260 Phenelizine, 1, 74 Pheneridine, 1, 301 Phenethicillin, 1, 410 Phenformin, 1, 75 Phenindandone, 1, 147 CUMULATIVE INDEX Pheniprazine, 1, 74 Pheniramine, 1, 77 Phenmetrazine, 1, 260 Phenobarbital, 1, 268 Phenomorphan, 1, 294 Phenoperidine, 1, 302 Phenoxybenzamine, 1, 55 Phenoxymethylpenicillin, 1, 410 Phensuximide, 1, 226 Phentermine, 1, 72 Phentolamine, 1, 242 Phenyl aminosalycilate, 2, 89 Phenylbutazone, 1, 236 Phenylephrine, 1, 63 Phenylglutarimide, 1, 257 Phenyltoloxamine, 1, 115 Phenyramidol, 1, 165 Pholcodeine, 1, 287 Phthaloyl sulfathiazole, 1, 132 Physostigmine, 1, 111 Piboserod, 7, 221 Picenadol, 4, 108 Piclamilast, 6, 41 Picumetrol, 5, 16 Pimetine, 2, 286 Piminodine, 1, 301 Pimobendan, 5, 117 Pimozide, 2, 290 Pinacidil, 4, 102 Pinadoline, 4, 202 Pindolol, 2, 342 Pinoxepin, 2, 419 Pioglitazone, 5, 74 Pipamazine, 1, 385 Pipamperone, 2, 288 Pipazethate, 1, 390 Pipecurium bromide, 4, 70 Piperacetazine, 1, 386 Piperacillin, 3, 207 Piperidolate, 1, 91 Piperocaine, 1, 13 Piperoxan, 1, 352 Pipobroman, 2, 299 Piposulfan, 2, 299 Pipradol, 1, 47 Piprandamine, 2, 459 Piprozolin, 2, 270 Piquindone, 4, 205 Piquizil, 2, 381 Pirazolac, 3, 138 Pirbencillin, 3, 207 Pirbuterol, 2, 280 Pirenperone, 3, 231 Piretanide, 3, 58 Pirexyl, 1, 115 Piridicillin, 1, 260 Piridocaine, 1, 13 Pirindol, 1, 45 Pirintramide, 1, 308 Piriprost, 4, 160 Piritrexim, 4, 169 Pirmagrel, 4, 161 Pirmenol, 3, 48 Piroctone, 3, 149 Pirodavir, 6, 101 Pirogliride, 3, 57 Pirolate, 3, 245 Piromidic acid, 2, 470 Piroxantrone, 5, 43 Piroxicam, 2, 394 Piroximone, 4, 94 Pirprofen, 2, 69 Pirqinozol, 3, 243 Pirsidomine, 6, 88 Pivampicillin, 1, 414 Pivopril, 4, Pizotyline, 2, 420 Plomestane, 5, 50 Pobilukast, 6, 37 Poldine mesylate, 2, 74 Polythiazide, 1, 360 Ponalrestat, 5, 132 Posaconazole, 7, 105 Practolol, 2, 106 Pralatrexate, 7, 211 Pramipexole, 6, 142 Pramoxine, 1, 18 Pranolium chloride, 2, 212 Prasurgel, 7, 189 Pravadoline, 5, 108 Prazepam, 2, 405 Praziquantel, 4, 213 Prazocin, 2, 382 Prednicarbate, 4, 71 Prednimustine, 3, 93 Prednisolone, 1, 192 265 266 CUMULATIVE INDEX Prednisolone acetate, 1, 192 Prednisone, 1, 192 Prednival, 2, 179 Prednylene, 1, 197 Premafloxacin, 6, 152 Prenalterol, 3, 30 Prenylamine, 1, 76 Pridefine, 3, 49 Prifelone, 5, 67 Prilocaine, 1, 17 Primidone, 1, 276 Primodolol, 3, 29 Prinomastat, 7, 54 Prinomide, 5, 64 Prinoxodan, 5, 130 Prizidilol, 3, 151 Probarbital, 1, 268 Probenecid, 1, 135 Probicromil, 4, 207 Probucol, 2, 126 Procainamide, 1, 14 Procaine, 1, Procarbazine, 2, 27 Procaterol, 3, 184 Prochlorperazine, 1, 381 Procinonide, 3, 94 Procyclidine, 1, 47 Prodilidine, 1, 305 Prodolic acid, 2, 459 Progabide, 4, 47 Progesterone, 2, 164 Proglumide, 2, 93 Proguanil, 1, 280 Prolintane, 1, 70 Promazine, 1, 377 Promethazine, 1, 373 Pronethalol, 1, 66 Prontosil, 1, 212 Propafenone, 5, 17 Propanidid, 2, 79 Propantheline bromide, 1, 394 Proparacaine, 1, 11 Propenzolate, 2, 75 Properidine, 1, 299 Propicillin, 1, 410 Propiomazine, 1, 376 Propionylpromazine, 1, 380 Propizepine, 2, 472 Propoxorphan, 3, 113 Propoxycaine, 1, 10 Propoxyphene, 1, 50 Propranolol, 1, 117 Propylhexedrine, 1, 37 Propylphenazone, 1, 234 Propylthiouracil, 1, 265 Proquazone, 2, 386 Proquinolate, 2, 368 Prorenone, 2, 175 Prostalene, 2, Prothipendyl, 1, 430 Protriptyline, 1, 152 Proxazole, 2, 271 Proxicromil, 4, 205 Pyrantel, 1, 266 Pyrathiazine, 1, 373 Pyrazineamide, 1, 277 Pyrilamine, 1, 51 Pyrimethamine, 1, 262 Pyrindamine, 1, 145 Pyrinoline, 2, 34 Pyrovalerone, 2, 124 Pyroxamine, 2, 42 Pyrrobutamine, 1, 78 Pyrrocaine, 1, 16 Pyrroliphene, 2, 57 Pyrroxan, 3, 191 Quazepam, 3, 196 Quazinone, 4, 212 Quazodine, 2, 379 Quazolast, 4, 216 Quetiapine, 6, 198 Quiflapon, 6, 130 Quilostigmine, 6, 195 Quinacrine, 1, 396 Quinapril, 4, 146 Quinazocin, 2, 382 Quinbolone, 2, 154 Quinelorane, 5, 167 Quinethazone, 1, 354 Quinfamide, 3, 186 Quinine, 1, 337 Quinodinium bromide, 2, 139 Quinpirole, 4, 205 Quinterol, 2, 366 CUMULATIVE INDEX Rabeprazole, 6, 140 Racemoramide, 1, 82 Racemorphan, 1, 293 Ragaglitazar, 7, 220 Ralitoline, 6, 81 Raloxifene, 5, 114 Raltitrexed, 6, 159 Raluridine, 6, 112 Ramelteon, 7, 72 Ramipril, 4, 84 Ranitidine, 3, 131 Ranolazine, 5, 94 Rasagiline, 6, 57 Reboxetine, 7, 61 Recainam, 4, 37 Reclazepam, 4, 153 Regadenson, 7, 197 Remifentanil, 5, 84 Remiprostol, 6, 56 Remoxipride, 4, 42 Repaglinide, 7, 15 Repirinast, 5, 175 Reproterol, 3, 231 Rescinnamine, 1, 319 Revaprazan, 7, 122 Ridogrel, 5, 80 Riluzole, 6, 142 Rimantidine, 2, 19 Rimcazole, 4, 201 Rimexolone, 5, 56 Rimiterol, 2, 278 Rimonabant, 7, 99 Riodipine, 4, 107 Rioprostil, 4, 13 Ripazepam, 3, 234 Risedronate, 6, 30 Risocaine, 2, 91 Risotilide, 5, 24 Risperidone, 5, 150 Ristianol, 4, 102 Ritodrine, 2, 39 Ritolukast, 5, 120 Ritonavir, 6, 12 Rivastigmine, 7, 66 Rivoglitazone, 7, 157 Rizatriptan, 6, 125 Rocastine, 5, 153 Rodocaine, 2, 450 Roflumilast, 7, 44 Rogletimide, 5, 81 Roletamide, 2, 103 Rolgamidine, 4, 80 Rolicyprine, 2, 50 Rolitetracycline, 1, 216 Rolodine, 2, 468 Romazarit, 5, 68 Ronidazole, 2, 245 Ropinirole, 6, 132 Ropitoin, 3, 139 Roquinimex, 6, 150 Rosoxacin, 3, 185 Rosuvastatin, 7, 124 Rotigotine, 7, 75 Rotoxamine, 2, 32 Roxatidine, 5, 26 Roxifiban, 6, 21 Rufinamide, 7, 108 Rupinavir, 7, Sabeluzole, 5, 86 Salbutamol, 2, 280 Salicylamide, 1, 109 Salmeterol, 5, 16 Salnacedin, 6, 49 Salsalate, 2, 90 Salvarsan, 1, 223 Sanfetrinem, 6, 165 Saperconazole, 6, 86 Saprisartan, 6, 123 Saquinavir, 6, Sarafloxacin, 5, 125 Sarmoxicillin, 3, 205 Sarpicillin, 3, 204 Secalciferol, 5, 59 Secobarbital, 1, 269 Sedoxantrone, 6, 203 Selfotel, 6, 99 Selodenoson, 7, 196 Sematilide, 5, 24 Semaxanib, 7, 149 Semustine, 2, 12 Seproxetine, 5, 25 Seratrodast, 6, 38 Serazepine, 5, 177 Sermetacin, 3, 166 Sertindole, 6, 129 267 268 CUMULATIVE INDEX Sertraline, 4, 57 Setoperone, 4, 172 Sezolamide, 5, 147 Sibopirdine, 6, 195 Sibutramine, 5, 25 Sildenafil, 6, 181 Sitafloxacin, 7, 174 Sitagliptan, 7, 206 Sivelstat, 7, 54 Solabegron, 7, 50 Solifenacin, 7, 171 Solypertine, 2, 342 Somantidine, 4, Sonepiprazole, 7, 166 Sontoquine, 1, 344 Sorivudine, 6, 111 Sotalol, 1, 66 Sotalol, 5, 23 Soterenol, 2, 40 Sparfloxacin, 5, 126 Spiradoline, 5, Spirapril, 4, 83 Spirilene, 2, 292 Spiromustine, 4, Spironolactone, 1, 206 Spiropiperone, 1, 306 Spiroplatin, 4, 16 Spirothiobarbital, 1, 276 Stanazole, 1, 174 Statine, 5, Stavudine, 6, 114 Stenbolone acetate, 2, 155 Styramate, 1, 219 Succinyl sulfathiazole, 1, 132 Sudoxicam, 2, 394 Sufentanil, 3, 118 Sufotidine, 5, 77 Sulazepam, 2, 403 Sulbactam pivoxil, 4, 180 Sulconazole, 3, 133 Sulfabenzamide, 2, 112 Sulfacarbamide, 1, 123 Sulfacetamide, 1, 123 Sulfachloropyridazine, 1, 124 Sulfacytine, 2, 113 Sulfadiazine, 1, 124 Sulfadimethoxine, 1, 125 Sulfadimidine, 1, 125 Sulfaethidole, 1, 125 Sulfaguanidine, 1, 123 Sulfaisodimidine, 1, 125 Sulfalene, 1, 125 Sulfamerazine, 1, 124 Sulfameter, 1, 125 Sulfamethizole, 1, 125 Sulfamethoxypyridine, 1, 124 Sulfamoxole, 1, 124 Sulfanilamide, 1, 121 Sulfanitran, 2, 115 Sulfaphenazole, 1, 124 Sulfaproxyline, 1, 123 Sulfapyridine, 1, 124 Sulfasalazine, 2, 114 Sulfasomizole, 1, 124 Sulfathiazole, 1, 124 Sulfathiourea, 1, 123 Sulfazamet, 2, 113 Sulfinalol, 3, 25 Sulfinpyrazone, 1, 238 Sulfisoxazole, 1, 124 Sulfonterol, 2, 42 Sulformethoxine, 1, 125 Sulfoxone, 1, 140 Sulindac, 2, 210 Sulnidazole, 2, 245 Suloctidil, 3, 26 Sulofenur, 5, 35 Sulopenem, 6, 167 Sulotraban, 5, 22 Sulpiride, 2, 94 Sulprostene, 3, Sulthiame, 2, 306 Sulukast, 5, 28 Sumarotene, 5, 37 Sumatriptan, 5, 108 Sunepitron, 7, 204 Sunitinib, 7, 150 Suporofen, 2, 65 Suricainide, 4, 49 Suritozole, 6, 88 Suronacrine, 5, 167 Symetine, 2, 29 Syrosingopine, 1, 319 Taclamine, 2, 224 Tacrine, 5, 166 CUMULATIVE INDEX Tadalafil, 7, 229 Talabostat, 7, 84 Talampicillin, 2, 438 Talnetant, 7, 168 Talniflumate, 3, 146 Talopram, 2, 357 Talsaclidine, 6, 105 Taltobulin, 7, 11 Taludipine, 5, 83 Tameridone, 5, 144 Tametraline, 3, 68 Tamibarotene, 7, 76 Tamoxifen, 2, 127 Tamoxifen, 5, 32 Tampramine, 4, 203 Tamsulosin, 6, 48 Tanaproget, 7, 178 Tandamine, 2, 347 Tandospirone, 5, 91 Tandutinib, 7, 183 Tanomastat, 7, 47 Tariquidar, 7, 167 Tasosartan, 6, 188 Tazadolene, 4, Tazarotene, 6, 148 Tazifylline, 4, 165 Tazobactam, 5, 156 Tazofelone, 6, 83 Tazolol, 2, 110 Tazomeline, 6, 198 Tebufelone, 5, 30 Tebuquine, 4, 28 Tecadenoson, 7, 195 Teclozan, 2, 28 Tegafur, 3, 155 Tegaserod, 7, 141 Telinavir, 6, Telmisartan, 6, 140 Teloxantrone, 6, 62 Temafloxacin, 5, 123 Tematropium, 5, 66 Temazepam, 2, 402 Temlastine, 4, 113 Temocapril, 6, 119 Temocillin, 4, 178 Temodox, 6, 160 Temozolomide, 6, 186 Tenidap, 5, 109 Tenofovir, 7, 197 Tenoxicam, 4, 173 Tepoxalin, 5, 68 Terazocin, 3, 194 Terbinafine, 4, 55 Terbogrel, 7, 60 Terconazole, 3, 137 Teriflumonide, 7, 93 Terlakiren, 5, Terolidine, 2, 56 Teroxirone, 4, 122 Tertrabenazine, 1, 350 Tesicam, 2, 379 Tesimide, 2, 296 Tesmilifene, 7, 58 Testolactone, 1, 160 Testosterone cypionate, 1, 172 testosterone decanoate, 1, 172 testosterone propionate, 1, 172 Tetomilast, 7, 101 Tetracaine, 1, 110 Tetracycline, 1, 212 Tetrahydrocannabinol, 1, 394 Tetrahydrozoline, 1, 242 Tetramisole, 1, 431 Tetrantoin, 1, 246 Tetrazolast, 5, 181 Tetroxyprim, 3, 154 Tetrydamine, 2, 352 Tezacitabine, 7, 131 Thalidomide, 1, 257 Thenium closylate, 2, 99 Theobromine, 1, 423 Theophylline, 1, 423 Thiabarbital, 1, 275 Thiabendazole, 1, 325 Thiabutazide, 1, 358 Thiamphenicol, 2, 45 Thiamprine, 2, 464 Thiamylal, 1, 274 Thiazinum chloride, 3, 240 Thiazolsulfone, 1, 141 Thiethylperazine, 1, 382 Thiofuradene, 1, 231 Thioguanine, 2, 464 Thiopental, 1, 274 Thiopropazate, 1, 383 Thioridazine, 1, 389 269 270 CUMULATIVE INDEX Thiothixene, 1, 400 Thonzylamine, 1, 52 Thozalinone, 2, 265 Thyromedan, 2, 79 Thyroxine, 1, 95 Tiaconazole, 3, 133 Tiacrilast, 4, 150 Tiacrilast, 5, 130 Tiagabine, 6, 101 Tiamenidine, 3, 137 Tiapamil, 4, 34 Tiaramide, 4, 134 Tiazofurin, 4, 96 Tibolone, 2, 147 Tibric acid, 2, 87 Ticabesone propionate, 4, 75 Ticarcillin, 2, 437 Ticlopidine, 3, 228 Ticolubant, 6, 96 Ticrynafen, 2, 104 Tidembersat, 7, 164 Tifurac, 5, 111 Tigemonam, 5, 155 Tigesterol, 2, 145 Tiletamine, 2, 15 Tilmacoxib, 7, 91 Tilomisole, 4, 217 Tilorone, 2, 219 Tiludronate, 6, 30 Timcodar, 7, 60 Timefurone, 4, 208 Timobesone propionate, 4, 75 Timolol, 2, 272 Tinabinol, 4, 210 Tiodazocin, 3, 194 Tioperidone, 3, 192 Tiopinac, 3, 238 Tiospirone, 5, 91 Tioxidazole, 3, 179 Tipentosin, 4, 129 Tipifarnib, 7, 192 Tiprednane, 4, 74 Tiprinast, 4, 173 Tiprinavir, 7, 120 Tipropidil, 3, 28 Tiquinamide, 2, 372 Tirapazamine, 6, 160 Tirilazad, 5, 61 Tirofiban, 6, 21 Tixanox, 3, 236 Tixocortol, 4, 73 Tizanidine, 6, 144 Tocainide, 3, 55 Tolamolol, 2, 110 Tolazamide, 1, 241 Tolbutamide, 1, 136 Tolcapone, 6, 41 Tolciclate, 3, 69 Tolgabide, 4, 47 Tolimidone, 3, 156 Tolindate, 2, 208 Tolmetin, 2, 234 Tolnaftate, 2, 211 Tolpyrramide, 2, 116 Tolrestat, 4, 56 Tolterodine, 7, 59 Toltrazuril, 5, 99 Tolvaptan, 7, 186 Tolycaine, 1, 17 Tomelukast, 5, 30 Tomoxetine, 4, 30 Tonazocine, 3, 115 Topiramate, 5, 90 Topixantrone, 7, 227 Topotecan, 5, 179 Topterone, 3, 88 Torborinone, 7, 172 Torcetrapib, 7, 169 Toremifene, 5, 33 Torsemide, 5, 82 Tosifen, 3, 62 Tosufloxacin, 5, 126 Tralonide, 2, 198 Tramadol, 2, 17 Tramazoline, 1, 243 Tranexamic acid, 2, Tranilast, 4, 44 Transcainide, 4, 112 Tranylcypromine, 1, 73 Travoprost, 7, 22 Trazodone, 2, 472 Trefentanil, 6, 102 Treloxinate, 2, 432 Trepipam, 4, 146 Trepostinil, 7, 81 Triacetamide, 2, 94 CUMULATIVE INDEX Triafungin, 3, 233 Triamcinolone, 1, 201 Triamcinolone acetonide, 1, 201 Triampyzine, 2, 298 Triamterine, 1, 427 Triazolam, 1, 368 Triazuryl, 2, 305 Trichlormethiazide, 1, 359 Triclonide, 2, 198 Trifenagrel, 4, 282 Triflocin, 2, 282 Triflubazam, 2, 406 Triflumidate, 2, 98 Trifluperidol, 1, 306 Triflupromazine, 1, 380 Trihexyphenidyl, 1, 47 Triiodothyronine, 1, 95 Trilostane, 2, 158 Trimazocin, 2, 382 Trimeprazine, 1, 378 Trimethadone, 1, 232 Trimethobenzamide, 1, 110 Trimethoprim, 1, 262 Trimethoquinol, 2, 374 Trimetozine, 2, 94 Trimetrexate, 4, 149 Trioxasalen, 1, 334 Trioxyfene, 3, 70 Tripamide, 4, 51 Tripelennamine, 1, 51 Triprolidine, 1, 78 Trofosfamide, 3, 161 Troglitazone, 6, 83 Tropanserin, 4, 39 Tropocaine, 1, Trovafloxacin, 6, 154 Troxacitabine, 7, 131 Tubulozole, 4, 91 Turosteride, 6, 65 Tybamate, 2, 22 Valacyclovir, 6, 182 Valdecoxib, 7, 92 Valsartan, 6, 23 Vandetanib, 7, 181 Vapiprost, 5, Vardefanil, 7, 205 Varespladib, 7, 144 Vedaprofen, 6, 58 Velnacrine, 5, 167 Venlafaxine, 5, 26 Verilopam, 3, 121 Verlukast, 5, 121 Verofylline, 2, 230 Vesnarinone, 5, 122 Vidagliptin, 7, 84 Viloxazine, 2, 306 Vinbarbital, 1, 269 Viprostol, 4, 13 Vofopitant, 7, 110 Volazocine, 2, 327 Voriconazole, 7, 103 Vorozole, 6, 144 Warfarin, 1, 131 Xamoterol, 4, 28 Xanomeline, 6, 98 Xanoxate, 3, 235 Xemilofiban, 6, 20 Xenalipin, 5, 19 Xilobam, 3, 56 Ximelagatran, 7, 16 Xipamide, 2, 93 Xorphanol, 4, 61 Xylamidine, 2, 54 Xylazine, 2, 307 Xylometazoline, 1, 242 Zacopride, 4, 42 Zafirlukast, 6, 130 Zalcitabine, 5, 98 Zaldaride, 6, 199 Zalepon, 6, 173 Zalospirone, 6, 117 Zaltidine, 4, 95 Zanamivir, 6, 95 Zankiren, 6, Zanoterone, 6, 65 Zatosetron, 5, 111 Zenarestat, 7, 184 Zeniplatin, 5, 12 Zidomethacin, 3, 166 Zifrosilone, 6, 42 Zileutron, 5, 113 271 272 CUMULATIVE INDEX Zimeldine, 3, 49 Zindotrine, 4, 168 Zinoconazole, 4, 92 Ziprasidone, 6, 134 Zofenopril, 4, 83 Zolamine, 1, 52 Zolamine, 1, 52 Zolazepam, 4, 174 Zoledronate, 6, 30 Zolmitriptan, 6, 126 Zolpidem, 4, 162 Zolpidem, 4, 83 Zolterine, 2, 301 Zoniclezole, 6, 137 Zopolrestat, 5, 132 Zosuquidar, 7, 79